If the bond between the restoration and the tooth structure is broken due to erosion or polymerization shrinkage of restorative materials, and if, under certain conditions, bacterial migration occurs within the marginal gap, then demineralization of tooth structure can be initiated. Diagnosis of such early demineralization adjacent to a restoration remains a subjective task that is complicated further when a microgap exists along the tooth-restoration interface. Radiographs often do not detect these recurrent lesions; currently, no better technique is available than removal of the restoration and direct visual examination for evidence of white sports or more advanced lesions. The long range goal of Project 4 is to develop a controlled-release system driven by the changes in the pH of the environment which can be incorporated as part of the restorative procedure for the caries diagnosis and/or protecting tooth structure adjacent to the restorations. This system should perform the following tasks when the pH of the environment reaches a critical value: a) signal the presence of early demineralization by releasing a distinct marker that the clinician can recognize; b) inhibit the continued colonization of this location by cariogenic bacteria and the resultant acid secretion in the microgap; c) initiate remineralization of the demineralized dentin. We will apply microsphere technology to achieve these goals. The advantages of microspheres are three-fold: 1) one can load various dyes as marker and therapeutic agents can be stored within the microspheres; 2) microspheres can be fabricated from various types of resin to form any desired release profile; and 3) the microspheres can be made to maintain their physical integrity even after complete release. During our current Center grant period, we have synthesized two main series of pH-sensitive plymers as release vehicles; Poly(styrene-co-vinylpridine) and poly(styrene-co-N,N,- diethylaminoethylmethacrylates). Agents which have been used to study release mechanisms include two dyes (9-aminoacridine and sodium flluorescein), mineralization enhancers such as sodium fluoride, and antibacterial agents such as chlorhexidine and fluoride ions. To understand the potential of the polymer as a controlled-release device and to facilitate formulation for delivering markers for caries diagnostic or bioactive agents to specific sites, we propose to study the effect of copolymer composition on agent loading and pH-stimulated release from microspheres. Often the microspheres need to incorporate some resin system to release agents to specific-sites. The effect of the resin system on the release from microspheres will also be determined. To improve the effectiveness of the diagnostic system an non-ionic water soluble dye will be made and tested. The ultimate goal of the Project 4 is to analyze release potential as a function of compositions in order to choose the ideal system for specific release rates. The use of polymer systems synthesized in other applications will be explored. For the effectiveness of the system, the release will also be tested for bactericidal release and fluoride ion release both in vitro and in bacterial culture. At year 04, we will conduct a feasibility study of the diagnostic system to generate preliminary data for future clinical studies.